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[Preprint]. 2025 Apr 17:2024.12.03.24318418.
doi: 10.1101/2024.12.03.24318418.

Probability of vertical HIV transmission: A systematic review and meta-regression

Magdalene K Walters  1 , Michelle A Bulterys  2   3 , Michael Barry  2 , Sarah Hicks  2 , Ann Richey  2 , Margalit Sabin  4 , Diana Louden  5 , Mary Mahy  6 , John Stover  7 , Robert Glaubius  7 , Hmwe Kyu  8 , Marie-Claude Boily  1 , Lynne Mofenson  9 , Kathleen Powis  10   11 , Jeffrey W Imai-Eaton  1   12
Affiliations

Probability of vertical HIV transmission: A systematic review and meta-regression

Magdalene K Walters et al. medRxiv. .

Update in

Abstract

Background: Eliminating HIV vertical transmission (VT) is a global priority and monitored by estimating paediatric HIV infections with the Joint United Nations Programme on HIV/AIDS supported Spectrum AIDS Impact Module (Spectrum-AIM). Recent innovations in antiretroviral therapy (ART) service delivery models and first-line regimens aimed to reduce VT probabilities. We conducted a systematic review and meta-analysis to estimate VT probabilities by maternal immunologic and treatment status.

Methods: We combined an updated systematic review with previous data in meta-regression models to estimate VT probabilities and determinants. We searched multiple databases for peer-reviewed English-language studies from all regions published between January 2018 and February 2024 with VT data stratified by maternal immunologic or treatment status from randomized trials, cohort, or observational studies. Four meta-regression models estimated VT probabilities. We assessed model sensitivity and compared estimates to Spectrum-AIM's previous results. Finally, we fit a meta-regression model to assess the association of ART class and initiation timing on viral load suppression (VLS) at delivery.

Findings: The updated review identified 24 new studies, yielding 110 total studies included in meta-regression analysis. For women not receiving ART, higher CD4 was associated with lower odds of perinatal VT (odds ratio [OR] 0.80 (95% CI: 0.75-0.84) per 100 CD4 cells/μL increase). For pregnant women on ART, each additional week on ART before delivery reduced odds of VT by 5.6% (3.2%-7.0%). The odds ratio of perinatal VT among pregnant women initiating integrase inhibitor-based ART 20 weeks pre-delivery was 0.36 (0.14-0.94) compared to those initiating non-nucleoside reverse transcriptase inhibitors (NNRTI)-based ART. This association was confounded by study region. Odds of VLS were lower when ART was initiated late in pregnancy (OR: 0.37 (0.21-0.68) for the reference regimen (NNRTI)), without significant difference by ART regimen.

Interpretation: VT probability varies by maternal immunologic stage, treatment regimen, and timing of treatment initiation. These estimates have been incorporated into Spectrum-AIM for UNAIDS 2025 HIV estimates. Earlier ART initiation is associated with higher odds of VLS at delivery. Further evidence is needed on the effects of recent ART innovations on VT outcomes.

Funding: NIH, UNAIDS, and UKRI.

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Conflict of interest statement

SH declares grants from NICHD F31HD116617 for work outside the submitted work. MCB declares funding from the NIH to HPTN and Wellcome Trust paid to her institution. MM is an employee of UNAIDS and received financial support through her institution. LM declares funding from ViiV to her employer (Elizabeth Glaser Pediatric AIDS Foundation) as well as paid consultancy fees from the WHO. KP declares funding from the National Institute of Health, Harvard T.H. Chan School of Public Health, and John Hopkins University paid to her institution. KP declares involvement on a data safety monitory board for Bifidobacterium infantis for Infant Immune Development, an RCT evaluating use of probiotics in infants (outside of submitted work). JWI-E declares grants from UNAIDS and Gates Foundation, consulting fees from BAO systems, and meeting travel support from UNAIDS, Gates Foundation, and International AIDS Society outside the submitted work. A preliminary analysis of this work was presented in October 2024 to a virtual meeting of the UNAIDS Reference Group on HIV Estimates, Modelling, and Projections.

Figures

Figure 1.
Figure 1.
PRISMA Flow Diagram for 2018–2024 review. Studies were excluded from previous reviews for the following reasons: A Not peer-reviewed (3), duplicate data (3), aggregates heterogenous results (1) B Not peer-reviewed (5), duplicate data (4), aggregates heterogeneous results (4) C Not peer-reviewed (2)
Figure 2.
Figure 2.. Data used in models one through four and model estimates of VT probability.
Point size reflects study size and colour indicates whether the study was identified in the 2024 systematic review. Blue violin plots are used for categorical models (model two and model four) and blue lines with ribbon are used for continuous models (model one and model three). Panels represent the different models used to produce estimates of VT probability compatible with Spectrum-AIM, with the top row displaying perinatal VT probabilities and the bottom row displaying breastfeeding VT probabilities.
Figure 3.
Figure 3.. Differences in 2023 number of paediatric infections using the Spectrum-AIM former vs. updated VT probabilities.
Coloured percentage points represent the percent difference between the infections using the former versus updated VT probabilities. Green and red percentages denote the relative percent increase and decrease in the number of infections between former and updated VT probabilities.
See this image and copyright information in PMC

References

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